Hyaluronic Acid-coated Polypeptide Nanogel Enhances Specific Distribution and Therapy of Tacrolimus in Rheumatoid Arthritis

Overview

Journal J Nanobiotechnology

Publisher Biomed Central

Specialty Biotechnology

Date 2024 Sep 5

PMID 39238027

Authors

Yuhuan Li

Xin Wang

Yu Gao

Ziyi Zhang

Te Liu

Zhuo Zhang

Yinan Wang

Fei Chang

Modi Yang

Affiliations

Soon will be listed here.

Abstract

Rheumatoid arthritis (RA) involves chronic inflammation, oxidative stress, and complex immune cell interactions, leading to joint destruction. Traditional treatments are often limited by off-target effects and systemic toxicity. This study introduces a novel therapeutic approach using hyaluronic acid (HA)-conjugated, redox-responsive polyamino acid nanogels (HA-NG) to deliver tacrolimus (TAC) specifically to inflamed joints. The nanogels' disulfide bonds enable controlled TAC release in response to high intracellular glutathione (GSH) levels in activated macrophages, prevalent in RA-affected tissues. In vitro results demonstrated that HA-NG/TAC significantly reduced TAC toxicity to normal macrophages and showed high biocompatibility. In vivo, HA-NG/TAC accumulated more in inflamed joints compared to non-targeted NG/TAC, enhancing therapeutic efficacy and minimizing side effects. Therapeutic evaluation in collagen-induced arthritis (CIA) mice revealed HA-NG/TAC substantially reduced paw swelling, arthritis scores, synovial inflammation, and bone erosion while suppressing pro-inflammatory cytokine levels. These findings suggest that HA-NG/TAC represents a promising targeted drug delivery system for RA, offering potential for more effective and safer clinical applications.

References

Kim J, Chung S, Pyo J, Chang S, Kim M, Park C . Methotrexate, leflunomide and tacrolimus use and the progression of rheumatoid arthritis-associated interstitial lung disease. Rheumatology (Oxford). 2022; 62(7):2377-2385. DOI: 10.1093/rheumatology/keac651. View

Ding H, Tan P, Fu S, Tian X, Zhang H, Ma X . Preparation and application of pH-responsive drug delivery systems. J Control Release. 2022; 348:206-238. DOI: 10.1016/j.jconrel.2022.05.056. View

Li C, Han Y, Luo X, Qian C, Li Y, Su H . Immunomodulatory nano-preparations for rheumatoid arthritis. Drug Deliv. 2022; 30(1):9-19. PMC: 9744217. DOI: 10.1080/10717544.2022.2152136. View

Wu J, Feng Z, Chen L, Li Y, Bian H, Geng J . TNF antagonist sensitizes synovial fibroblasts to ferroptotic cell death in collagen-induced arthritis mouse models. Nat Commun. 2022; 13(1):676. PMC: 8813949. DOI: 10.1038/s41467-021-27948-4. View

Liu Y, Wang M, Liu W, Jing J, Ma H . Olaparib and Doxorubicin Co-Loaded Polypeptide Nanogel for Enhanced Breast Cancer Therapy. Front Bioeng Biotechnol. 2022; 10:904344. PMC: 9108339. DOI: 10.3389/fbioe.2022.904344. View

Komatsu N, Takayanagi H . Mechanisms of joint destruction in rheumatoid arthritis - immune cell-fibroblast-bone interactions. Nat Rev Rheumatol. 2022; 18(7):415-429. DOI: 10.1038/s41584-022-00793-5. View

Amruta A, Iannotta D, Cheetham S, Lammers T, Wolfram J . Vasculature organotropism in drug delivery. Adv Drug Deliv Rev. 2023; 201:115054. PMC: 10693934. DOI: 10.1016/j.addr.2023.115054. View

Marinho A, Nunes C, Reis S . Hyaluronic Acid: A Key Ingredient in the Therapy of Inflammation. Biomolecules. 2021; 11(10). PMC: 8533685. DOI: 10.3390/biom11101518. View

Yang Y, Guo L, Wang Z, Liu P, Liu X, Ding J . Targeted silver nanoparticles for rheumatoid arthritis therapy via macrophage apoptosis and Re-polarization. Biomaterials. 2020; 264:120390. DOI: 10.1016/j.biomaterials.2020.120390. View

10.

Fereig S, El-Zaafarany G, Arafa M, Abdel-Mottaleb M . Tacrolimus-loaded chitosan nanoparticles for enhanced skin deposition and management of plaque psoriasis. Carbohydr Polym. 2021; 268:118238. DOI: 10.1016/j.carbpol.2021.118238. View

11.

Di Matteo A, Bathon J, Emery P . Rheumatoid arthritis. Lancet. 2024; 402(10416):2019-2033. DOI: 10.1016/S0140-6736(23)01525-8. View

12.

Feng N, Guo F . Nanoparticle-siRNA: A potential strategy for rheumatoid arthritis therapy?. J Control Release. 2020; 325:380-393. DOI: 10.1016/j.jconrel.2020.07.006. View

13.

Fearon U, Hanlon M, Floudas A, Veale D . Cellular metabolic adaptations in rheumatoid arthritis and their therapeutic implications. Nat Rev Rheumatol. 2022; 18(7):398-414. DOI: 10.1038/s41584-022-00771-x. View

14.

Zhao W, Liang Z, Yao Y, Ge Y, An G, Duan L . GGT5: a potential immunotherapy response inhibitor in gastric cancer by modulating GSH metabolism and sustaining memory CD8+ T cell infiltration. Cancer Immunol Immunother. 2024; 73(7):131. PMC: 11096297. DOI: 10.1007/s00262-024-03716-3. View

15.

Smolen J . Insights into the treatment of rheumatoid arthritis: A paradigm in medicine. J Autoimmun. 2020; 110:102425. DOI: 10.1016/j.jaut.2020.102425. View

16.

Xu Z, Liu G, Liu P, Hu Y, Chen Y, Fang Y . Hyaluronic acid-based glucose-responsive antioxidant hydrogel platform for enhanced diabetic wound repair. Acta Biomater. 2022; 147:147-157. DOI: 10.1016/j.actbio.2022.05.047. View

17.

Li Z, Xu W, Yang J, Wang J, Wang J, Zhu G . A Tumor Microenvironments-Adapted Polypeptide Hydrogel/Nanogel Composite Boosts Antitumor Molecularly Targeted Inhibition and Immunoactivation. Adv Mater. 2022; 34(21):e2200449. DOI: 10.1002/adma.202200449. View

18.

Wang J, Xu W, Zhang N, Yang C, Xu H, Wang Z . X-ray-responsive polypeptide nanogel for concurrent chemoradiotherapy. J Control Release. 2021; 332:1-9. DOI: 10.1016/j.jconrel.2021.02.003. View

19.

Ding L, Zhang P, Huang X, Yang K, Liu X, Yu Z . Intracellular Reduction-Responsive Molecular Targeted Nanomedicine for Hepatocellular Carcinoma Therapy. Front Pharmacol. 2022; 12:809125. PMC: 8784786. DOI: 10.3389/fphar.2021.809125. View

20.

Smith M, Berman J . What Is Rheumatoid Arthritis?. JAMA. 2022; 327(12):1194. DOI: 10.1001/jama.2022.0786. View